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March 03, 2015; 84 (9) Article

Parkinson disease with REM sleep behavior disorder

Features, α-synuclein, and inflammation

Yang Hu, Shu-Yang Yu, Li-Jun Zuo, Chen-Jie Cao, Fang Wang, Ze-Jie Chen, Yang Du, Teng-Hong Lian, Ya-Jie Wang, Piu Chan, Sheng-Di Chen, Xiao-Min Wang, Wei Zhang
First published February 6, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001308
Yang Hu
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Shu-Yang Yu
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Li-Jun Zuo
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Chen-Jie Cao
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Fang Wang
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Ze-Jie Chen
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Yang Du
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Teng-Hong Lian
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Ya-Jie Wang
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Piu Chan
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Sheng-Di Chen
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Xiao-Min Wang
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Wei Zhang
From the Departments of Neurology (Y.H., S.-Y.Y., L.-J.Z., C.-J.C., F.W., Z.-J.C., Y.D., T.-H.L., W.Z.) and Geriatrics (S.-Y.Y., W.Z.), and Core Laboratory for Clinical Medical Research (Y.-J.W.), Beijing Tiantan Hospital, Capital Medical University, Beijing; China National Clinical Research Center for Neurological Diseases (W.Z., P.C., S.-D.C., X.-M.W.), Beijing; Center of Parkinson's Disease (W.Z., P.C., S.-D.C., X.-M.W.), Beijing Institute for Brain Disorders; Beijing Key Laboratory on Parkinson Disease (W.Z., P.C., S.-D.C., X.-M.W.); Department of Neurology and Neurobiology (P.C.), Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing; Department of Neurology (S.-D.C.), Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; and Department of Physiology (X.-M.W.), Capital Medical University, Beijing, China.
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Full PDF
Citation
Parkinson disease with REM sleep behavior disorder
Features, α-synuclein, and inflammation
Yang Hu, Shu-Yang Yu, Li-Jun Zuo, Chen-Jie Cao, Fang Wang, Ze-Jie Chen, Yang Du, Teng-Hong Lian, Ya-Jie Wang, Piu Chan, Sheng-Di Chen, Xiao-Min Wang, Wei Zhang
Neurology Mar 2015, 84 (9) 888-894; DOI: 10.1212/WNL.0000000000001308

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Abstract

Objectives: To investigate clinical features and potential mechanisms involving α-synuclein oligomer and inflammation in patients with Parkinson disease (PD) and probable REM sleep behavior disorder (PRBD).

Methods: We used the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) to evaluate patients with PD and classified each as PRBD or not probable (NPRBD). Data collection included demographic information and evaluation of clinical symptoms using a series of rating scales. We tested for α-synuclein oligomer and inflammatory factors in CSF and serum. Data analyses included comparisons between PRBD and NPRBD groups and correlation analyses among RBDSQ score and levels of the above factors.

Results: The frequency of PRBD in patients with PD was 30.67%. The PRBD group had longer disease duration, more advanced disease stage, more severe motor symptoms, and other more severe nonmotor symptoms, including depression, anxiety, and fatigue. Levels of α-synuclein oligomer in CSF and serum in the PRBD group were elevated compared with NPRBD and control groups. RBDSQ score was increased with the elevated α-synuclein oligomer level in CSF, interleukin 1β and nitric oxide levels in CSF, and prostaglandin E2 level in serum in the PD group. The level of α-synuclein oligomer in CSF was enhanced with the deterioration of motor symptoms, and the elevated levels of interleukin 1β, nitric oxide, and tumor necrosis factor α in CSF in the PRBD group.

Conclusions: PRBD is common in patients with PD, especially those with longer disease duration and more severe motor and nonmotor symptoms. Elevated α-synuclein levels in CSF and serum may be correlated with PRBD through inflammation in central and peripheral nervous systems.

GLOSSARY

ESS=
Epworth Sleepiness Scale;
FSS=
Fatigue Severity Scale;
HAMA=
Hamilton Anxiety Scale;
HAMD=
Hamilton Depression Scale;
H-Y=
Hoehn and Yahr;
IL-1β=
interleukin 1β;
MMSE=
Mini-Mental State Examination;
NO=
nitric oxide;
NPRBD=
not probable REM sleep behavior disorder;
PD=
Parkinson disease;
PGE2=
prostaglandin E2;
PQSI=
Pittsburgh Quality of Sleep Index;
PRBD=
probable REM sleep behavior disorder;
RBD=
REM sleep behavior disorder;
RBDSQ=
REM Sleep Behavior Disorder Screening Questionnaire;
SCOPA-AUT=
Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms;
SN=
substantia nigra;
TNF-α=
tumor necrosis factor α;
UPDRS-III=
Unified Parkinson's Disease Rating Scale, Part III

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received June 8, 2014.
  • Accepted in final form October 20, 2014.
  • © 2015 American Academy of Neurology
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